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Published online before print February 22, 2005

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(Journal of Leukocyte Biology. 2005;77:811-819.)
© 2005 by Society for Leukocyte Biology

Accumulation of an intron-retained mRNA for granulocyte macrophage-colony stimulating factor receptor common ß chain in neutrophils of myelodysplastic syndromes

Yayoi Shikama^*,,1, Tsutomu Shichishima, Isao Matsuoka^*, Paul T. Jubinsky, Colin A. Sieff and Yukio Maruyama

^* Department of Pharmacology and
First Department of Internal Medicine, Fukushima Medical University, Japan;
Section of Pediatric Hematology/Oncology, Albert Einstein College of Medicine, Bronx, New York; and
Department of Pediatric Oncology and Hematology, Dana-Farber Cancer Institute, Boston, Massachusetts

¹ Correspondence: Department of Pharmacology and First Department of Internal Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan. E-mail: yayois{at}fmu.ac.jp

We recently identified a reduction in the neutrophil surface expression of common ß chain (ßc) of the receptor for granulocyte macrophage-colony stimulating factor (GM-CSF) in the patients with myelodysplastic syndromes (MDS). To determine the etiology of the impaired ßc expression, ßc mRNA from neutrophilic granulocytes of MDS patients and healthy controls was analyzed by a combination of direct reverse transcriptiase-polymerase chain reaction-based single-strand conformational polymorphism and sequencing. Nine different ßc transcripts were detected, but none was specific for MDS. However, one of the transcripts (ßc79) containing a 79-base intron insertion between exons V and VI was significantly increased in MDS. This 27-kd isoform consisted of the ßc N-terminal 182 amino acids followed by a new 84-amino-acid sequence. ßc79 was overexpressed in all MDS subtypes. No genomic mutations were detected within the intron or at the intron/exon boundaries. The isoform is predominantly located in the cytoplasm by Western blot analysis and was unable to generate high-affinity binding sites or transduce a signal for proliferation when coexpressed with the receptor for human GM-CSF chain. Our study suggests that the accumulation of the abnormal ßc transcripts with intron V retention results in the reduction in cell-surface expression of ßc observed in MDS.

Key Words: MDS • GM-CSF receptor • ßc • splice variant • intron retention